Stimulation of the metastatic properties of lewis‐lung‐carcinoma cells by autologous granulocyte‐macrophage colony‐stimulating factor

Abstract

Using both polymerase-chain-reaction analysis and the soft-agar colony-forming unit assay, granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to be expressed by cloned metastatic Lewis-lung-carcinoma (LLC-LN7) cells but not by non-metastatic LLC-C8 cells. Furthermore, the metastatic LLC-LN7 cells were shown to respond both to autologous GM-CSF and to exogenous recombinant GM-CSF (rGM-CSF). In the presence of neutralizing anti-GM-CSF antibodies, the metastatic LLC cells became less able to migrate or to adhere and invade through a reconstituted basement membrane. Moreover, the addition of rGM-CSF further enhanced the capacity of the metastatic LLC cells to adhere to the reconstituted basement membrane. This stimulation of metastatic properties of the LLC cells by either autologous or exogenous GM-CSF was associated with enhanced endogenous protein phosphorylation. Two proteins of approximately Mr 45,000 and Mr 64,000 were the dominant target proteins to be phosphorylated by the presence of GM-CSF. These results suggest that autologous GM-CSF may function as an autocrine stimulator of the metastatic properties of metastatic LLC cells.

Expression and function of colony-stimulating factors and their receptors in human prostate carcinoma cell lines

“…A relevant example of a cell type whose metastatic and migratory actions are dependent upon GM-CSF is Lewis lung carcinoma. GM-CSF is produced by a metastatic strain of these cells, but not by a nonmetastatic strain; neutralizing anti-GM-CSF antibodies decrease the ability of the metastatic strain to undergo migration and invasion [50]. Cellular migratory capability may be an important biological parameter: Partin et al [51] have obtained evidence that a malignant prostate cell's migratory ability correlates with its metastatic potential.…”

Autocrine Growth Regulation by Granulocyte Colony-Stimulating Factor and Granulocyte Macrophage Colony-Stimulating Factor in Human Gliomas with Tumor Progression

“…Young et al 51 described a stimulation of the migratory and metastatic potential in Lewis lung carcinoma cells by GM-CSF. Others showed the association of GM-CSF expression with a metastatic phenotype in solid tumors of mouse and human origin.…”

Growth-factor-dependent migration of human lung-cancer cells

“…The main finding of our study is that IGF I, IGF II, HGF, EGF and SCF stimulate cell migration of human non-SCLC cell lines in a dose-dependent manner. Even though rhGM-CSF, synthetic hCGRP, bombesin, bovine insulin and rhIL-6 have been shown to stimulate migration of normal and tumor cells (Ruff et al, 1985;Sanghavi et al, 1994;Sehgal and Tamm, 1991;Shoji et al, 1990;Young et al, 1992;Kohn et al, 1990), they did not stimulate motility in the lung-cancer cell lines examined by us.…”

“…IGF II induced both chemotactic and chemokinetic motility and, in vivo, may play a role in the local invasive action of tumor cells, possibly acting in an autocrine and/or a paracrine fashion. The growth and motility of established mesothelioma and lung-cancer cell lines is stimulated by various growth factors (Klominek et al, 1998a,b;Young et al, 1992). In addition, we have shown that certain factors stimulate autocrine motility in the Wart cell line (Klominek et al, 1998c).…”

“…A number of chemotactic factors, including growth factors and ECM-components, are required for continued migration, through either autocrine or paracrine pathways. Growth factors, known to promote cell migration, are produced by a variety of normal and malignant cells, e.g., granulocyte-macrophage-colony-stimulating factor (GM-CSF) (Young et al, 1992), interleukin-6 (IL-6) (Sehgal and Tamm, 1991), bombesin (Ruff et al, 1985), insulin-like growth factors I and II (IGF I and IGF II) (Kohn et al, 1990), hepatocyte growth factor (HGF) (Klominek et al, 1998b), epidermal growth factor (EGF) (Engebraaten et al, 1993;Li et al, 1994), stem-cell factor (SCF) (Sekido et al, 1993), calcitonin-gene-related peptide (CGRP) (Sanghavi et al, 1994) and insulin (Kohn et al, 1990). The concept of autocrine stimulation of tumor-cell migration was first proposed by Liotta et al (1986), whose in vitro experiments showing that factors produced by tumor cells could elicit both chemotactic and chemokinetic responses in the producer cells (see also Stracke et al, 1992).…”